Original Article
Involvement of the interferon-γ–induced T cell–attracting chemokines, interferon-γ–inducible 10-kd protein (CXCL10) and monokine induced by interferon-γ (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome
Noriyoshi Ogawa,
Li Ping, Li Zhenjun, Yukiko Takada, Susumu Sugai,
Corresponding Author
Noriyoshi Ogawa
Kanazawa Medical University, Ishikawa-ken, Japan
Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa-ken 920-0293, JapanSearch for more papers by this authorNoriyoshi Ogawa,
Li Ping, Li Zhenjun, Yukiko Takada, Susumu Sugai,
Corresponding Author
Noriyoshi Ogawa
Kanazawa Medical University, Ishikawa-ken, Japan
Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa-ken 920-0293, JapanSearch for more papers by this authorAbstract
Objective
To elucidate the mechanism of the development of T cell infiltrates in the salivary glands of patients with Sjögren's syndrome (SS), we studied T cell–attracting chemokines and their receptors.
Methods
The expression of the T cell–attracting chemokines, interferon-γ (IFNγ)–inducible 10-kd protein (IP-10; also called CXCL10), monokine induced by IFNγ (Mig; also called CXCL9), and stromal cell–derived factor 1 (SDF-1; also called CXCL12), in salivary glands from SS patients was investigated by polymerase chain reaction–enzyme-linked immunosorbent assay (ELISA). Cells that produce chemokines and lymphocytes that express chemokine receptors were identified by immunohistochemistry. The production of IP-10 and Mig proteins by salivary epithelial cells in response to IFNγ was determined by ELISA.
Results
Expression of IP-10 and Mig messenger RNA (mRNA) was significantly up-regulated in SS salivary glands compared with normal salivary glands (both P < 0.01). There was no significant difference in SDF-1 mRNA expression between the SS and normal salivary glands. IP-10 and Mig proteins were predominantly expressed in the ductal epithelium adjacent to lymphoid infiltrates. Most of the CD3+ infiltrating lymphocytes in dense periductal foci expressed CXCR3, the receptor for IP-10 and Mig. IFNγ induced the production of high levels of IP-10 and Mig proteins from cultured SS salivary epithelial cells.
Conclusion
These findings suggest that IFNγ stimulates the production of IP-10 and Mig in the SS ductal epithelium, and that IP-10 and Mig are involved in the accumulation of T cell infiltrates in the SS salivary gland. Chemokines or chemokine receptors could be a rational new therapeutic target in SS.
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